Biomaterials in the form of fibers find applications in surgical sutures, woven medical devices such as vascular grafts, and tissue engineering scaffolds, among others. Fibrous scaffolds are attractive in tissue engineering for their inherent advantages, including high surface area for cell attachment and controlled porous architecture. Conventional fiber fabrication procedures require heat or denaturing solvents. Incorporation of biological materials in these fibrous scaffolds have therefore been limited or difficult. We propose to use the interracial polyelectrolyte complexation technique to fabricate fibers that can possess biofunctionalities of encapsulated growth factors and surface-immobilized ligands. Interfacial polyelectrolyte complexation is a process of self-assembly that occurs when two oppositely charged polyelectrolytes come together. Taking place in aqueous solutions, the process is mild enough for encapsulation or immobilization of proteins into the fibers. Such fibers would be particularly attractive for tissue engineering applications, where optimal tissue engineering requires more than an inert scaffold to serve merely as a substrate for cell attachment and cell growth. Cues or signal molecules in the form of adhesion molecules, growth and differentiation factors, or even plasmid DNA, should be incorporated into these scaffolds in a spatially defined manner to orchestrate the growth of new tissue. We propose to understand the mechanism of fiber formation by evaluating the critical parameters of polymer composition, concentration of the oppositely charged polyelectrolytes, temperature, charge density, and fiber draw rate. Fibers will be synthesized based on water-soluble chitin or chitosan as the polycation, and alginate or heparin as the polyanion. The structure- property relationship of these fibers will be established by determining their physical, chemical, and biology properties. We will introduce biofunctionalities into the fibers by encapsulating drugs, proteins, DNA nanoparticles, as well as decorating the fiber surface with streptavidin to allow attachment of biotinylated ligands. Finally we will evaluate the cell behavior of primary hepatocytes cultured on a non-woven mesh of these biofunctional fibers. It is expected that findings in this proposal will produce novel biofunctional fibrous biomaterials with interesting biomedical applications.